Is FAT1 p.Pro930Ser (c.2788C>T) pathogenic?

FAT1 p.Pro930Ser (c.2788C>T) is classified Uncertain significance in FAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with FAT1 p.Pro930Ser (c.2788C>T)?

FAT1 p.Pro930Ser (c.2788C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FAT1 p.Pro930Ser (c.2788C>T) in the general population?

FAT1 p.Pro930Ser (c.2788C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about FAT1 p.Pro930Ser (c.2788C>T)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

FAT1 p.Pro930Ser

c.2788C>T · rs777211440 · VCV3093054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.48, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 97 kb · p 0.42 · regional, not allelic
Overall
CADD	13.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,996 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00136% 22/1,613,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.0032%	31,232
European (non-Finnish)	0.0011%	90,761
South Asian	0.0011%	91,078

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FAT1
Protein: p.Pro930Ser
Coding: c.2788C>T
MANE Select: NM_005245
dbSNP: rs777211440
Type: single nucleotide variant
Location: chr4:186707040 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI <0.01 (gnomAD)
Residue 930: the cadherin 8 domain

Full FAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FAT1 p.Ala1663Thr Uncertain significance ★★ same condition
FAT1 p.Ala1862Ser Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala2046Thr Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala2502Asp Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala3007Val Uncertain significance ★★ same condition
FAT1 p.Ala3437Thr Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala3913Ser Uncertain significance ★★ ⚠ same condition
FAT1 p.Ala4042Ser Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fat1-p-pro930ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown